The primary aim of this study is to further examine the effects of hypokalemia and hypernatremia on the blood perfused working heart of the dog. In some animals the changes will be produced locally by interposing a blood dialyzer in the left common coronary artery. Experiments already completed indicate that local hypokalemia initially increases both myocardial contractile force and coronary vascular resistance and that local hypokalemia enhances the increased force seen with local hypernatremia. In an attempt to shed light on mechanism, these responses will be examined before and after the administration of propranolol. In other animals, the time course of the contractile force, coronary blood flow, coronary sinus PO2, cardiac oxygen consumption, and ionic flux responses to local hypokalemia and to local hypokalemia plus hypernatremia will be examined by prolonging exposure time to two hours. In still others, hypokalemia and hypokalemia plus hypernatremia will be generalized throughout all of the blood by transferring the dialyzer to the femoral vessels and cardiac response will be examined by monitoring the same variables as in the local studies. Since there is evidence that low potassium concentration eventually leads to decreased contractility and a waning of the increase in coronary resistance, tissue levels of high energy phosphates and venous concentration of adenosine will be examined in the guinea pig heart. Secondary aims of this study are to examine cardiac responses to localized and generalized hyponatremia, hypocalcemia and hypomagnesemia. In addition to providing basic information on the role of cations in function of the intact blood perfused working heart, these studies may be relevant to certain experimental cardiomyopathies and to disease states in man which produce hypokalemia, hypernatremia and other electrolyte abnormalities. BIBLIOGRAPHIC REFERENCES: Brace, R.A., J. B. Scott, W. T. Chen, D. K. Anderson and F. J. Haddy. Direct effects of hypoosmolality on vascular resistance and myocardial contractile force. Proc. Soc. Exptl. Biol. and Med. 148:578, 1975. Bunger, R., F. J. Haddy and E. Gerlach. An isolated guinea pig heart preparation with in vivo-like features. Pflugers Arch. 353:317, 1975. drg*